Objective: To investigate the impact of time since injury on neuropsychological and psychosocial outcome after serious TBI in childhood or adolescence. Methods: The subjects were eight patients with serious TBI sustained at a mean age of 14 years who had been assessed neuropsychological at one, seven and 14 years after TBI. A retrospective longitudinal design was chosen to describe the development in six neuropsychological domains on basis of the assessments. Psychosocial data were gathered from clinical knowledge and a semi-structured interview at 14 years after TBI. Results: Performance of verbal IQ shows a declining trend over the three assessments, that the performance of attention and working memory is low and that verbal learning is the cognitive domain, which exhibits the largest impairments. The main psychosocial result is that three of the eight subjects go from a school situation with no adjustments to adult life with an early retirement. Conclusions: Time since insult is an important factor when assessing outcome after TBI in childhood and adolescence and that assessment of final outcome should not be done before adulthood.

Aim: The objective of this thesis was to find genes and chromosomal regions involved in neuroblastoma (NB) tumor progression. NB is a childhood tumor of the sympathetic nervous system that generally occurs spontaneously. Biologically, NB has a complex heterogeneity from tumor progression to tumor regression, dependent on clinical stage and age at diagnosis. The main genetic markers, which are also of prognostic value in NB, are amplification of the oncogene MYCN, deletion of chromosome arm 1p and gain of chromosome arm 17q. Results: We have been shown using fluorescence in situ hybridization (FISH) on a Scandinavian tumor material, that 17q gain is present in approximately 65% of all NB stages, is significantly associated with poor prognosis and predicts survival. The gene encoding somatostatin receptor 2 (SSTR2), localized in chromosome region 17q24, was not found to be mutated in any NB, when analyzed with PCR-based single stranded conformation polymorphism/heteroduplex (SSCP/HD) and DNA sequencing. In a tentative effort of defining of the location of a general embryonal tumor suppressor gene (TSG) on 1p, we combined the smallest region of overlap (SRO) of 1p deletions in NB tumors and germ cell tumors (GCTs). We thus delimited the NB/GCT SRO to approximately 5 cM between markers D1S508 and D1S244, and fine-mapped this region by radiation hybrid mapping and construction of a bacterial artificial chromosome (BAC) contig. A homozygously deleted region in an NB cell line was found to partially overlap the proximal part of the 5 cM-SRO defined by us, which further focused our search for a TSG to a 500 kb candidate region in 1p36.22. Two attractive candidate NB TSGs, DFFA and CASP9, are both located in 1p36.2 and encode key apoptotic mediators. In fact, DFFA resides in the 500 kb TSG candidate region. Via sequence analysis of the entire tumor material, we found three different coding alterations in DFFA which all affect the highly conserved N-terminal regulatory domain of DFF45. Using RT-PCR and real-time RT-PCR (TaqMan) studies, we were able to show that both DFFA and CASP9 are preferably expressed in NB tumors with favorable outcome. It has been proposed that lack of apoptosis plays an important role in tumor progression. We therefore screened an array with cDNAs involved in the apoptotic process, to find genes differentially expressed in NB tumors with unfavorable versus favorable biology. Using real-time RT-PCR analysis, we verified the differential expression of several transcripts encoding mitochondrial apoptotic mediators. Conclusions: We have shown that 17q gain is the most frequently detected alteration in NB and that it is associated with established prognostic factors. We narrowed down the TSG candidate region on 1p and found mutations in a gene localized in the region possessing fundamental functions in apoptosis. Our results also suggest that the mitochondrial apoptotic pathway is suppressed at multiple steps in advanced stages of NB tumors, due to imbalance between anti-apoptotic and pro-apoptotic mediators.

DFF45 has essential functions in the final stage of apoptosis by acting both as a folding chaperone and a DNase inhibitor of DFF40. The gene encoding DFF45 (DFFA) maps to the consensus deleted region in primary neuroblastoma (NB; 1p36.2-3) and within the homozygously deleted region in an NB cell line (1p36.2). DFF45 is therefore an attractive candidate NB tumor suppressor. In a previous study we found a rare allele variant, causing a non-polar to a polar amino acid exchange (Ile69Thr) in a preserved hydrophobic patch of DFF45, and we also found DFFA to be preferentially expressed in favorable NB tumors. We have extended the previous study and performed mutation analyses in another 56 NB tumors (100 in total) as well as a set of other tumors for coding mutations in DFFA. We have also performed studies of the DFFA expression in tumors using real-time PCR. We found a missense mutation (Ile15Met) in the remaining allele of a teratoma with heterozygous deletion of 1p, and a three base-pair deletion in an NB of unknown stage causing a deletion of amino acid 37 in DFF45. The one-base substitution detected in the teratoma was not present in the patients constitutional DNA, i.e. it is a true mutation present in the tumor DNA only. In conclusion, three different coding alterations have been found in the region encoding the N-terminal regulatory domain of DFF45, responsible for binding and achieving its chaperone and inhibitor functions on other proteins. Moreover, by real-time RT-PCR expression study, we found the mRNA level of DFFA to be significantly (p=0.038) reduced by a factor of 1.7 times in NB tumors of unfavorable outcome.

This paper analyzes the welfare effects of improved health status through increased water quality using a choice experiment. The survey was administered to a random sample of households in metropolitan Cairo, Egypt. We apply a random parameter logit model in the analysis and illustrate the richness of information that can be obtained from this type of model by estimating individual level willingness to pay (WTP). We find a significant WTP for improved health status, both for short-run and long-run health effects. However, the estimated WTP is fairly low compared with the costs of a program that would achieve these improvements.

In this paper the applicability of the Industrial Network Approach, during the age of Information and Communication Technology (ICT) has been examined. Both primary and secondary data are collected and analyzed with the help of the industrial network approach. Our results have shown that the network approach can be applied as it is to a large extent, however, some of the existing concepts have to be modified and some new concepts have to be developed so that approach will be a useful and adequate tool to promote our understanding of how industrial markets functions and are structured.

Two cauliform bacteria (CM243T and CM251) isolated by J. Poindexter from the Atlantic Ocean were characterized by 16S rRNA gene sequencing, TaqI restriction fragment length polymorphism and single-strand conformation polymorphism analyses of the internally transcribed 16S-23S rDNA spacer (ITS1) region, analysis of fatty acids from cellular lipids, mass spectrometry of polar lipids and physiological properties. The two strains showed very low diversity of polar lipids with diacyl-sulfoquinovosyl glycerols as the predominant lipids. The two bacterial strains were observed to have nearly identical 16S rRNA gene sequences and could not be differentiated by their ITS1 regions. The isolates differed from species of the genus Maricaulis by their 16S rRNA gene sequences, polar lipids and fatty acid patterns. On the basis of the genotypic analyses and estimations of phylogenetic similarities, physiological and chemotaxonomic characteristics, it is proposed that the isolates represent a new genus and species, for which the name Woodsholea maritima gen. nov., sp. nov. (type strain CM243T=VKM B-1512T=LMG 21817T) is proposed.

OBJECTIVE: To validate a proposed model (Berglundh et al. 2003) and to evaluate the rate and degree of osseointegration at turned (T) and sand blasted and acid etched (SLA) implant surfaces during early phases of healing. MATERIAL AND METHODS: The devices used for the study of early healing had a geometry that corresponded to that of a solid screw implant with either a SLA or a T surface configuration. A circumferential trough had been prepared within the thread region (intra-osseous portion) that established a geometrically well-defined wound chamber. Twenty Labrador dogs received totally 160 experimental devices to allow the evaluation of healing between 2 h and 12 weeks. Both ground and decalcified sections were prepared from mesial/distal and buccal/lingual device sites. Histometric and morphometric analyses of the ground sections and morphometric analysis of the tissue components in decalcified sections were performed. RESULTS: The ground sections provided an overview of the various phases of tissue formation, while the decalcified, thin sections enabled a more detailed study of events involved in bone tissue modeling and remodeling for both SLA and T surfaces. The initially empty wound chamber became occupied with a coagulum and a granulation tissue that was replaced by a provisional matrix. The process of bone formation started already during the first week. The newly formed bone present at the lateral border of the cut bony bed appeared to be continuous with the parent bone, but on the SLA surface woven bone was also found at a distance from the parent bone. Parallel-fibered and/or lamellar bone as well as bone marrow replaced this primary bone after 4 weeks. In the SLA chambers, more bone-to-device contact, more initial woven bone and earlier lamellar bone formation was found than in the T chambers. CONCLUSION: Osseointegration represents a dynamic process both during its establishment and its maintenance. While healing showed similar characteristics with resorptive and appositional events for both SLA and T surfaces, the rate and degree of osseointegration were superior for the SLA compared with the T chambers.